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Neuroinflammation has emerged as a central pathology common to several acute and chronic brain diseases. Recent studies have displayed the anti-inflammatory properties of naturally occurring compounds derived from mushrooms and plants could potentially reduce neuroinflammation and disease progression. In this study, we aimed to investigate the impact of psilocybin and eugenol, as well as their combinations, on neuroinflammation. To induce inflammation through the gut-brain axis, we employed a colitis mouse model via oral feeding of dextran sulfate sodium (DSS). By administering various concentrations and combinations of treatments, both before and after inducing inflammation, we sought to assess the synergistic anti-inflammatory effects of psilocybin and eugenol. Our findings revealed oral psilocybin and eugenol post-treatment significantly reduced the expression of pro-inflammatory cytokines and inflammatory mediators in the brain, including IL-1β, IL-6, and COX-2. Notably, combined treatment of psilocybin and eugenol exhibited the strongest reduction in IL-6 levels when compared to the DSS group. While both psilocybin and eugenol possess anti-inflammatory effects, the combined treatment overall did not demonstrate synergistic reductions in neuroinflammation across all markers. This study adds to the growing body of evidence supporting the therapeutic potential of psilocybin and eugenol in psychiatric and neurodegenerative inflammatory disorders. Further research is necessary to elucidate the underlying mechanisms of their anti-inflammatory effects and to evaluate their efficacy in clinical settings. • Dextran sulfate sodium induced neuroinflammation through the gut-brain axis. • Pretreatment with psilocybin and/or eugenol did not prevent neuroinflammation. • Post-treatment with psilocybin and/or eugenol decreased neuroinflammation. • Psilocybin and eugenol post-treatment demonstrated the most promising results. • Psilocybin and eugenol demonstrate dose-dependent synergy. [ABSTRACT FROM AUTHOR]

The longer splice isoforms of vascular endothelial growth factor-A (VEGF-A), including mouse VEGF164, contain a highly basic heparin-binding domain (HBD), which imparts the ability of these isoforms to be deposited in the heparan sulfate-rich extracellular matrix and to interact with the prototype sulfated glycosaminoglycan, heparin. The shortest isoform, VEGF120, lacks this highly basic domain and is freely diffusible upon secretion. Although the HBD has been attributed significant relevance to VEGF-A biology, the molecular determinants of the heparin-binding site are unknown. We used site-directed mutagenesis to identify amino acid residues that are critical for heparin binding activity of the VEGF164 HBD. We focused on basic residues and found Arg-13, Arg-14, and Arg-49 to be critical for heparin binding and interaction with extracellular matrix in tissue samples. We also examined the cellular and bio-chemical consequences of abolishing heparin-binding function, measuring the ability of the mutants to interact with VEGF receptors, induce endothelial cell gene expression, and trigger microvessel outgrowth. Induction of tissue factor expression, vessel outgrowth, and binding to VEGFR2 were unaffected by the HBD mutations. In contrast, the HBD mutants showed slightly decreased binding to the NRP1 (neuropilin-1) receptor, and analyses suggested the heparin and NRP1 binding sites to be distinct but overlapping. Finally, mutations that affect the heparin binding activity also led to an unexpected reduction in the affinity of VEGF164 binding specifically to VEGFR1. This finding provides a potential basis for previous observations suggesting enhanced potency of VEGF164 versus VEGF120 in VEGFR1-mediated signaling in inflammatory cells. [ABSTRACT FROM AUTHOR]

The L-type amino acid transporter-1 (LAT-1) has been associated with tumor growth. Using cDNA microarrays, overexpression of LAT-1 was found in 87.5% (7/8) of esophageal adenocarcinomas relative to 12 Barrett's samples (33% metaplasia and 66% dysplasia) and was confirmed in 100% (28/28) of Barrett's adenocarcinomas by quantitative reverse transcription polymerase chain reaction. Immunohistochemistry revealed LAT-1 staining in 37.5% (24/64) of esophageal adenocarcinomas on tissue microarray. LAT-1 also transports the amino acid-related chemotherapeutic agent, melphalan. Two esophageal adenocarcinoma and one esophageal squamous cell line, expressing LAT-1 on Western blot analysis, were sensitive to therapeutic doses of melphalan (P < .001). Simultaneous treatment with the competitive inhibitor, BCH [2-aminobicyclo-(2,1,1)-heptane-2-carboxylic acid], decreased sensitivity to melphalan (P < .05). In addition, confluent esophageal squamous cultures were less sensitive to melphalan (P < .001) and had a decrease in LAT-1 protein expression. Tumors from two esophageal adenocarcinoma cell lines grown in nude mice retained LAT-1 mRNA expression. These results demonstrate that LAT-1 is highly expressed in a subset of esophageal adenocarcinomas and that Barrett's adenocarcinoma cell lines expressing LAT-1 are sensitive to melphalan. LAT-1 expression is also retained in cell lines grown in nude mice providing a model to evaluate melphalan as a chemotherapeutic agent against esophageal adenocarcinomas expressing LAT-1. [ABSTRACT FROM AUTHOR]

Tris(pentamethylphenyl)gallium, (Me5C6)3Ga, was prepared by reaction of pentamethylphenylmagnesium bromide with gallium(III) chloride in diethyl ether. The title compound, characterized by 1H and 13C NMR, elemental analyses, and single crystal X-ray diffraction, crystallizes in the P1¯ (No. 2) space group with a=9.003(9) A˚, b=10.713(1) A˚, c=16.066(2) A˚, α=107.63 (3)°, β=97.63 (3)°, γ=90.08(3)°, for Z=2. Refinement converged at R1=0.050, wR2=0.11. The pentamethylphenyl ligands are configured about the gallium center in a propeller fashion at angles of 67.3°, 62.3°, and 60.9°. [Copyright &y& Elsevier]

In psoriatic lesions, epidermal keratinocytes overexpress vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) and transforming growth factor alpha (TGF-α). TGF-α has been shown to induce VEGF/VPF in normal human epidermal keratinocytes in vitro. By using a 19-mer antisense phosphorothioate oligodeoxynucleotide (PS-ODN) complementary to bases 6-24 relative to the translational start site of the VEGF/VPF mRNA, the control sense and mismatched PS-ODNs, we examined modulation of VEGF/VPF induction by TGF-α in vitro. Normal human epidermal keratinocytes were treated with PS-ODNs and Lipofectin for 8 h prior to the addition of TGF-α. Inhibition was assayed at the level of secreted protein by capture ELISA and mRNA expression was assayed by Northern blot analysis. The anti-sense PS-ODN was capable of inhibiting VEGF/VPF RNA and protein to near-basal levels. This inhibition was concentration dependent. No effect was observed with the sense or mismatch con- trol PS-ODNs. These studies suggest that antisense oligonucleotide technology may be a potential therapy for the inhibition of angiogenesis associated with certain skin disorders such as psoriasis. [ABSTRACT FROM AUTHOR]

• Synthesis of new Zwitterionic ligands derived from N -Heterocyclic Carbenes (NHCs). • Coordination chemistry of Zwitterionic ligands to copper(I) and silver(I). • Spectroscopic and structural characterization of four novel structures. N -Heterocyclic Carbene (NHC) ligands have been instrumental in the synthesis of novel metal and main group-containing compounds, as well as their subsequent reactivity. Here, the coordination chemistry of CS 2 and PhNCS derivatives of the sterically encumbering 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene (IPr) are studied. The reaction of IPr•CS 2 with Cu(I) and Ag(I) salts results in the isolation of dinuclear complexes, [(IPr•CS 2) 2 M 2 (THF) n ][X] 2 , M = Cu, X = PF 6 , n = 4; M = Ag, X = OTf, n = 2. The 1:1 stoichiometric reaction of IPr•PhNCS with CuI results in to the formation of ([IPr•PhNCS) 2 Cu][CuI 2 ]. All complexes were characterized by 1H, 13C, and IR spectroscopy and their solid-state structures determined by X-ray crystallography. [ABSTRACT FROM AUTHOR]